Increased mononuclear cell tissue factor and type-2 plasminogen activator inhibitor and reduced plasma fibrinolytic capacity in children with lymphoma
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N Semeraro1, P Montemurro, P Giordano
1Dipartimento di Scienze Biomediche e Oncologia Umana, Università di Bari, Italy.
Insights
Lymphoma patients show increased blood clotting factors and reduced fibrinolysis. Mononuclear cells in lymphoma patients produce more procoagulant activity and plasminogen activator inhibitor, contributing to clotting activation.
Area of Science:
- Hematology
- Oncology
- Biochemistry
Background:
- Blood clotting and fibrin deposition are frequently observed in lymphoma patients.
- Understanding the mechanisms behind these hemostatic changes is crucial for patient management.
Purpose of the Study:
- To evaluate the procoagulant activity (PCA) and plasminogen activator inhibitor (PAI) production by peripheral blood mononuclear cells in children with lymphoma.
- To compare plasma levels of key hemostatic factors between lymphoma patients and healthy controls.
Main Methods:
- Assessed PCA and PAI activity in mononuclear cells cultured from 12 lymphoma patients and 12 healthy donors.
- Measured plasma antigen levels of tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), PAI-1, PAI-2, and D-dimer.
Main Results:
- Mononuclear cells from lymphoma patients exhibited significantly higher PCA (tissue factor-dependent) and PAI activity/PAI-2 antigen levels.
- Patients showed elevated plasma PAI-1 and t-PA antigen levels, with PAI-1 significantly higher than t-PA.
- Markedly increased plasma D-dimer levels were observed in lymphoma patients, indicating in vivo clotting activation.
Conclusions:
- Monocytes in lymphoma patients display functional abnormalities, leading to simultaneous expression of tissue factor and antifibrinolytic activity.
- These cellular and plasma abnormalities, along with reduced fibrinolytic potential, likely contribute to the prothrombotic state in lymphoma.
Abstract:
Blood clotting activation and fibrin deposition are common findings in lymphoma patients. We evaluated the capacity of peripheral blood mononuclear cells to produce procoagulant activity (PCA) and plasminogen activator inhibitor (PAI) in 12 children with newly diagnosed lymphoma (8 non-Hodgkin's, 4 Hodgkin's) and in 12 matched healthy donors. In the same subjects we also measured plasma antigen levels of tissue-type PA (t-PA), urokinase-type PA (u-PA), PAI-1, PAI-2, and D-dimer. PCA generated by mononuclear cells after incubation for 20 h at 37 degrees C was significantly higher in patients than in controls (p = 0.027). In all samples it was identified as tissue factor by functional criteria (dependence on factor VII). Moreover, culture medium obtained from patients' mononuclear cells after incubation for 20 h at 37 degrees C contained significantly higher amounts of PAI activity and PAI-2 antigen than control samples (p < 0.001). Plasma PAI-1 and t-PA antigens were significantly augmented in patients (p < 0.005), the mean increase of PAI-I being about 5 times higher than that of t-PA. Plasma levels of D-dimer were markedly increased in the patient's group (p < 0.001), whereas u-PA and PAI-2 antigens did not differ from controls. It is suggested that monocytes from lymphoma patients are endowed with functional abnormalities leading to the simultaneous expression of tissue factor and antifibrinolytic activity. These abnormalities, coupled with a reduced plasma fibrinolytic potential, could play an important pathogenetic role in blood clotting activation and fibrin deposition associated with lymphoma.